Ambient mass spectrometry is a recent advancement in the field of analytical chemistry and has allowed for the analysis of samples with little-to-no sample preparation. Based on this concept, a variety of ambient ionization methods have been introduced, including desorption electrospray ionization (DESI), direct analysis in real time (DART), desorption atmospheric pressure chemical ionization (DAPCI), electrospray-assisted laser desertion/ionization (ELDI), matrix-assisted laser desorption electrospray ionization (MALDESI), extractive electrospray ionization (EESI), atmospheric solids analysis probe (ASAP), jet desorption ionization (JeDI), desorption sonic spray ionization (DeSSI), desorption atmospheric pressure photoionization (DAPPI), plasma-assisted desorption ionization (PADI), and dielectric barrier discharge ionization (DBDI).
DESI is a representative method for ambient mass spectrometry. It has been shown to be useful in providing a rapid and efficient means of desorbing and ionizing a variety of target compounds of interest under ambient conditions. A variety of analytes (for example, pharmaceuticals, metabolites, drugs of abuse, explosives, chemical warfare agents, and biological tissues) have all been studied with these ambient ionization methods.
In U.S. Pat. No. 7,915,579, DESI has been shown to analyze liquid samples without sample preparation and may be used for ionizing both small molecules and large biomolecules, such as proteins. Still, it would be useful to use the liquid DESI apparatus in combination with liquid chromatography for the analysis of mixtures; however, the high flow rates associated with some chromatography techniques, such as high performance liquid chromatography (“HPLC”), tend to overwhelm the conventional ion source, such as electrospray ionization (ESI).
Furthermore, after analyte separation by chromatography, some analytes are difficult to ionize; therefore, it is often necessary to include post-column derivatization. Typically, the protocol for derivatization is to introduce a chemical reagent solution that merges with the chromatographic eluent via a Tee mixer. Such a mixing causes an increased time delay for MS ionization, leading to peak broadening resulting from diffusion effects.
In addition, integration of electrochemical cells into a LC/MS system will broaden the application of LC/MS. Conventionally, the coupling of EC with MS has been accomplished with ionization methods such as thermospray (TS), fast atom bombardment (FAB), and electrospray ionization (ESI). In particular, the latter method is useful in ionizing non-volatile products or intermediates of electrochemical reactions. However, in coupling EC with ESI, the EC system needs to be electrically floated, or decoupled, from the ionization source to separate the high voltage operation of the ionization source from the low voltage operation of the EC cell. This decoupling increases the complexity of the apparatus and the methods of analysis. Also, in coupling EC with ESI-MS there is a limitation that the solvent for electrolysis in EC must be compatible with ESI ionization. The combination of DESI with the EC system has been shown in U.S. patent application Ser. No. 12/558,819, published as Application Publication No. 2010/0258717, the disclosure of which is incorporated herein by reference in its entirety.
Still, there remains a need for improving the performance of LC/MS to tolerate high flow elution rate of LC without a limitation in selecting a solvent for LC mobile phase and electrolysis, online post-column derivatization, and easy integration of EC cells into the LC/MS systems for broader application.